rs56164683

Positions:

• chr1-10306707-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000377083.5(KIF1B):​c.*2060A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 857,810 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (40 hom., cov: 25)
  • Exomes 𝑓: 0.025 (263 hom.)
• Consequence: KIF1B ENST00000377083.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

RN7SL731P (HGNC:46747): (RNA, 7SL, cytoplasmic 731, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2769/140902) while in subpopulation NFE AF= 0.0286 (1877/65718). AF 95% confidence interval is 0.0275. There are 40 homozygotes in gnomad4. There are 1355 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2769 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF1B	NM_001365951.3	c.2115+9461A>G		intron_variant		ENST00000676179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF1B	ENST00000676179.1	c.2115+9461A>G		intron_variant			NM_001365951.3	P1
RN7SL731P	ENST00000584329.2	n.243A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2769 AN: 140802 Hom.: 40 Cov.: 25

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.0169

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00976

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000978

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0123

GnomAD4 exome AF: 0.0255 AC: 18252 AN: 716908 Hom.: 263 Cov.: 10 AF XY: 0.0256 AC XY: 8539 AN XY: 333626

Gnomad4 AFR exome AF: 0.00315

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.00629

Gnomad4 EAS exome AF: 0.000217

Gnomad4 SAS exome AF: 0.00174

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0273

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0197 AC: 2769 AN: 140902 Hom.: 40 Cov.: 25 AF XY: 0.0199 AC XY: 1355 AN XY: 67964

Gnomad4 AFR AF: 0.00482

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00976

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000978

Gnomad4 FIN AF: 0.0479

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0122

Alfa AF: 0.0208 Hom.: 7

Bravo AF: 0.0156

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56164683; hg19: chr1-10366765;